Multiple endocrine neoplasia type 2 (MEN2) is a type of multiple endocrine neoplasia syndrome (MENS) that causes tumours to develop in two or more endocrine glandsglands responsible for the production and secretion of hormones. Endocrine glands are responsible for the production and secretion of hormones, and help to control many vital bodily functions.
Familial cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs syndromes, also known as hereditary cancer syndromes, are rare conditions that cause an increased riskthe possibility that something bad will happen of cancer as the result of inherited genetic mutations in certain cancer-related genes. They can affect both adults and children, however they generally develop in people at a younger age than normal. While familial cancer syndromes are not classified as cancer, they are equally as severe and can be life-threatening as they are associated with the development of various tumours throughout the body. Having a familial cancer syndrome does not guarantee the development of cancer, however the risk of developing cancer is higher than those who do not have a familial cancer syndrome.
Neuroendocrine cancers are a complex group of tumours that develop in the neuroendocrine system, which is responsible for regulating important bodily functions such as heart rate, bloodthe red bodily fluid that transports oxygen and other nutrients around the body pressure and metabolism. They most commonly develop in the gastro-intestinal tract, pancreasa long, flat organ that sits between the stomach and the spine that plays a key role in digestion and blood sugar regulation, and the lungs; however, they can develop anywhere in the body. These tumours develop from neuroendocrine cellsthe basic structural and functional unit of all living things, which are responsible for receiving signals from the nervous system and producing hormones and peptides (small proteins) in response.
There are four primary types of MENS, which vary based on tumoura tissue mass that forms from groups of unhealthy cells location and genetic mutations involved: MEN1, MEN2 (type 2A and type 2B (also known as MEN3)), MEN4 and MEN5. This page will focus on MEN2, including MEN2A and MEN2B.
MEN2 is generally diagnosed equally among the sexes, and is generally diagnosed in childhood. However, anyone can develop this disease.
Types of MEN2
MEN2 can be classified into two distinct subtypes based on the types of tumours present and the endocrine glands affected.
MENS Type 2A (MEN2A)
MENS type 2A (MEN2A) is the most common subtype of MEN2, and involves a medullary thyroid carcinomacancer arising from tissues that line organs in addition to one or both of the following NETs:
MEN2A can also be categorised into four subvariants, based on the presence or absence of other conditions:
- Classical MEN 2A (no associated condition present).
- MEN2A with cutaneous lichen amyloidosis.
- MEN2A with Hirschsprung disease.
- Familial medullary thyroid cancer (without pheochromocytoma or parathyroid enlargement/tumours).
MEN 2A is generally diagnosed equally between the sexes, and is often more prevalent in children.
MENS Type 2B (MEN2B)
MENS type 2B (MEN2B), which may also be referred to as MENS type 3 (MEN3), is the rarer subtype of MEN2, and involves a more severe presentation of medullary thyroid carcinoma in addition to pheochromocytomas. These tumours do not involve a parathyroid tumour, and are generally more aggressive.
MENS 2B is generally diagnosed equally between the sexes, and is often more prevalent between the ages of 5-18.
For more information on medullary thyroid carcinoma, please refer to the Rare Cancers Australia Medullary Thyroid cancer page.
Treatment
When cancers are detected, they are staged and graded based on size, metastasiswhen the cancer has spread to other parts of the body, also known as mets, and how the cancer cells look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas and grading helps your doctors determine the best treatment for you. However, each patient with MEN2 will present with a unique disease behaviour, with varying tumour locations and symptoms. As such, there is no one treatment method that will work for everyone, and there is no standard staging system for this disease. Instead of staging and grading, your doctor will recommend a treatment plan based on the following factors:
- Type of tumours present.
- Whether the tumours are malignantcancerous, may grow and spread to other areas of the body (cancerous) or benignnot cancerous, can grow but will not spread to other body parts (non-cancerous).
- Tumour location.
- Whether or not malignant tumours have metastasised.
- Your age.
- General health.
- Your treatment preferences.
Your doctor may also recommend genetic testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Treatment options for tumours associated with MEN2 may include:
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence to remove as much of the tumour(s) as possible – this will vary based on tumour location.
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells.
- Targeted therapymedication that targets specific molecular features of cancer cells.
- Watch and waitthe close monitoring of a cancer without giving treatment until symptoms appear or worsen.
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
Cancer Screening
Once a diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of MEN2 has been confirmed, implementing a targeted screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening plan becomes essential due to the increased risk of developing certain cancers. The content of this plan will vary from person to person based on the genetic mutation involved, your family’s history of cancer and the types of cancers that may be present. It will also outline the routine tests you should have and how regularly you should have them. For patients with MEN2, the screening guidelines differ between MEN2A and MEN2B.
MEN2 Screening Guidelines
For people with MEN2A, screening guidelines may include:
- Annual physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Blood test measuring calcitonin levels annually beginning at 3-5 years old.
- Will also be required three months after a thyroidectomycomplete or partial removal of the thyroid gland, and may be required more frequently in those with residual medullary thyroid carcinoma.
- Blood test measuring carcinoembryonic antigen (CEA) levels three months after a thyroidectomy, then annually (more frequently in those with residual medullary thyroid carcinoma).
- Metanephrine levels (either via a 24-hour urine test or blood test) annually beginning at 11-16 years old.
- MRI and/or CT scan of adrenal glands if metanephrine results are abnormal.
- Blood test measuring calcium and/or ionised calcium levels annually beginning at 11-16 years old.
MEN2B Screening Guidelines
For people with MEN2B, screening guidelines may include:
- Annual physical examination.
- Blood test measuring calcitonin levels annually beginning at six years old.
- Will also be required three months after a thyroidectomy, and may be required more frequently in those with residual medullary thyroid carcinoma.
- Blood test measuring carcinoembryonic antigen (CEA) levels three months after a thyroidectomy, then annually (more frequently in those with residual medullary thyroid carcinoma).
- Metanephrine levels (either via a 24-hour urine test or blood test) annually beginning at 11 years old.
- MRI and/or CT scan of adrenal glands if metanephrine results are abnormal.
Screening options for MEN2 may evolve as new technologies are developed and our understanding of the condition grows. It is essential to discuss your individual circumstances with your healthcare team to determine the most appropriate screening plan for you.
Risk factors
MEN2 is caused by a genetic mutation in the RET proto-oncogenea type of gene that normally regulates cell growth and division, but when mutated can cause uncontrollable cell growth and may lead to cancer on chromosome 10, which plays a crucial role in cell growth and proliferation. It is an autosomal dominant disease, which means you have a 50% chance of developing the condition if one of your parents carries the genetic mutation.
Symptoms
The symptoms of MEN2 often vary by the type(s) of tumours present. General symptoms of MEN2 may include:
- Painless lump in the neck.
- Difficulty swallowing.
- Dyspneadifficulty breathing, shortness of breath.
- Changes in the voice, such as hoarseness.
- Lymphadenopathyswollen lymph nodes/glands, also known as adenopathy in the neck.
- Hypertensionhigh blood pressure.
- Headaches.
- Tachycardiaa rapid heart rate; clinically defined as a rate of more than 100 beats per minute.
- Unexplainable sweatiness.
- Polyuriafrequent urination.
- Constipationa condition where a person has difficulty passing faeces/stools.
- Hormonea chemical substance produced by glands in the endocrine system that regulates various functions in the body abnormalities.
Symptoms related to specific tumours can be found on our knowledgebase.
Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.
Diagnosis
If your doctor suspects you have tumours associated with MEN2, they may order some of the following tests to confirm the diagnosis and refer you to a specialist for treatment. The tests required for diagnosis will often vary based on the symptoms present, and where the tumour(s) are suspected to be located.
- Physical examination.
- Genetic testing.
- Endocrine studiesstudies that involve blood, urine and/or imaging tests to analyse hormone levels.
- Imagingtests that create detailed images of areas inside the body tests, potentially including:
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- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
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- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
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- PET (positron emission tomography) scana type of medical imaging that uses radioactive tracers to create detailed images of the body.
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- Ultrasounda type of medical imaging that uses soundwaves to create detailed images of the body .
- Biopsyremoval of a section of tissue to analyse for cancer cells.